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2012 Grants - Reed

Effects of Risk Factors on Tau-Mediated Memory Deficits

Miranda N. Reed, Ph.D.
West Virginia University
Morgantown, West Virginia

2012 New Investigator Research Grant

The protein tau normally helps maintain the structure of brain cells. This protein is modified by a process called phosphorylation, or the adding of phosphate molecules. But in the earliest stages of Alzheimer's disease, tau becomes excessively phosphorylated and loses its ability to carry out normal functions. Such "hyperphosphorylated" tau tends to accumulate into tangles that can hinder cell-to-cell communication in the brain. Moreover, current research suggests that hyperphosphorylated tau may exert its toxicity even before tangle formation.

Miranda N. Reed, Ph.D., and colleagues have been studying the effects of abnormal tau in mice that are engineered to develop symptoms of frontotemporal dementia (FTD)—a disorder closely related to Alzheimer's. They found that toxic tau accumulated inside the animals' dendritic spines. These structures are extensions of brain cells that help the cells send chemical messages to one another. Dr. Reed's team was able to link this "mislocation" of tau to early brain cell degeneration in the mice.

For their proposed grant, Dr. Reed and colleagues will extend their earlier work by studying the effects of diabetes on tau phosphorylation. Recent findings have shown that high blood sugar levels, a key diabetic hallmark, can cause hyperphosphorylation. So the investigators propose to develop a mouse model that develops both Alzheimer's-like symptoms and diabetes. This model should enable them to determine more conclusively whether abnormal tau accumulates in dendritic spines—and whether such accumulation leads to brain cell damage and cognitive loss. The researchers will also assess how aging can promote tau-related Alzheimer's symptoms in their mice. Overall, the results of this study could shed new light on tau's role in the earliest stages of brain disease. Such work could lead to novel preventative therapies.